Study On The Construction And Performance Of Wet Tissue Adhesive Hydrogel Inspired By Mussel Adhesive Protein

Adhesives hydrogels,which are kinds of soft materials composed of three-dimensional（3D）polymer networks and water,have emerged as promising candidates for wound dressing,drug delivery,tissue repair,surgery,trauma hemostasis,and so on owing to their high moisture content,excellent flexibility,and cell compatibility characteristics.However,most conventional adhesives hydrogels lack wet tissue adhesion ability and easily fall off during use,which cannot meet clinical needs.In recent years,learning from this intriguing mussels-inspired wet adhesion,much research interest has been paid to the understanding of underlying interaction mechanisms as well as exploiting numerous tough adhesion hydrogel.In this work,inspired by the wet adhesion mechanism of mussels,the use of natural extracts has successfully developed a hydrogel with underwater tissue adhesion ability.Mechanical properties,adhesion properties of the hydrogel were systematically studied,and then systematically explored the relationship between hydrophobic alkyl chain,charge,and cohesion and adhesion energy,the mechanism of action of hydrogel and tissue.The main research contents and results are as follows:1.Based on the mussel adhesion mechanism and nano-enhanced hydrogel mechanism,a strong polyacrylamide-tannic acid-kaolin（PAAm-TA-KA）hydrogel with tissue adhesion ability was designed in accordance with polyacrylamide-tannic acid（PAAm-TA）hydrogels.In the hydrogels,TA was applied as not only a chemical cross-linker,but a provider for adhesive catechol groups for wet adhesion;in addition,KA not only acted a physical cross-linker,but a hemostatic accelerator.The research shows that there are a large number of non-covalent（hydrogen bonds,π-πinteraction,cation-π）in the PAAm-TA-KA3 hydrogel network,which play a role in energy dissipation.Therefore the fracture stress of the hydrogel relative to PAAm-TA increased by 60%.The abundant catechol groups on tannic acid endow the hydrogels with strong and durable adhesion strength of up to 0.48 MPa on porcine skin.The hemostatic time of the PAAm-TA-KA3 hydrogel on the rat femoral artery model was reduced to 24 s from148 s of the control,resulting from the hydrogel’s intimately adhesion to tissue to seal the bleeding wound,and from the blood coagulation accelerating potential of the KA nanoparticles.In order to explore the universal applicability of the PAAm-TA system,an organic/containing catechol group tissue adhesive(T_x%H_y%PAM)hydrogel consisting of acrylamide（AAm）,tannic acid（TA）,and hydroxyapatite（HAP）and KCl was facilely fabricated.In the hydrogel,organic phase of the TA and AAm serves as binding sites while hard inorganic phase of HAP acts as reversible cross-linkages to enhance the cohesion strength and toughness of the hydrogel.They exhibit high mechanical properties（tensile strength of 0.46 MPa,compressive strength up to 10.15 MPa,toughness of441.23 k J/m³）,and robust adhesiveness（adhesion strengths to porcine skin with 420 k Pa）.Importantly,the robust hemostatic ability may be attributed to the adjacent TA-HAP providing an adaptive cooperation effect between catechol and Ca²⁺.The blood loss for the T_3%H_0.75%PAM hydrogels was 0.15 g in hemorrhaging liver mouse model,which was88.9%lower that of the control group Furthermore,the hydrogel with KCl electrolyte is good ionic conductors,so they can also be used for human strain sensors.2.So far,the porcine skin adhesion strength of the catechol-containing hydrogels is far less than that of cartilage.Here,chitosan（CS）,3-（（8,11,13）-pentadeca-trienyl）benzene-1,2-diol（UCAT）and acrylic acid（AA）are used as raw materials to prepare underwater tissue selective adhesive（P（AA-co-UCAT）-CS）hydrogel.Due to the covalent/electrostatic attraction/π–π/cationic–π/hydrogen bonding,and the hydrophobic interaction from the long hydrophobic alkyl chain of the catechol derivative,the hydrogel has a strong mechanical property,i.e.,tensile stress,fracture strain,tearing energy and fracture toughness of 0.57 MPa,2510%,1854 J/m²,and 6620 J/m²,respectively.Its adhesion energy to porcine skin and to blooded porcine skin was 1664 J/m²and 1011J/m²,respectively.After being placed for 30 days,its adhesion energy with pigskin can still be maintained at 1400 J/m²,which proves that the catechol groups in the hydrogel are not easily oxidized to weaken its tissue adhesion energy.For later wound treatment,we spray a weak alkaline solution（p H=8.0）on the hydrogel/pigskin interface to break the adhesion bonds of the interface and easily debond the hydrogel from the tissue surface.The research results show that the key factors that affect the adhesion performance of P（AA-co-UCAT）-CS hydrogels on tissues are the chemical properties of the groups in the hydrogel network,bulk energy dissipation,the capability of forming topological structures,and the destroying or removing interfacial water.Along with the strong toughness and tearing energy of the hydrogel bulk,can dissipate a large amount of energy,thereby amplifying the adhesion energy.In other words,the hydrogel with appropriate components exhibited excellent adhesive performance due to the balanced cohesion and adhesion.The long hydrophobic alkyl chains in the PUCAT moieties expel or destroy the hydration layer on the skin surface to facilitate the adhesion of the hydrogel to the skin.The hydrogel contains tissue-adhesive catechol groups,which can covalently interact with the–NH₂and–SH groups,formπ-πand cation-πinteractions with the phenyl group and cation,and form hydrogen bonding with the-OH,-NH₂,and-COOH groups on the porcine skin surface.The-COOH groups of the PAA units in the hydrogel form hydrogen bonding and electrostatic interactions with groups on the skin surface.Interfacial chain interlocking,some short chains or chain ends may diffuse into the skin tissue to become entangled with the molecular chains in the tissue,which acts like a staple suture to stitch the hydrogel and skin tissue.3.Due to of the difference in osmotic pressure,Conventional adhesive hydrogels inevitably“swell”under water or physiological conditions,which seriously weakens their mechanical properties and adhesion energy,limiting their applications in biomedicine.On the basis of P（AA-co-UCAT）-CS hydrogel,N-vinyl-2-pyrrolidinone（NVP）was introduced to prepare ANUC hydrogel.We try to strategies on the control of swelling focus on the regulation of the strong and high-density cross-linkings.So that the hydrogel tends to be stable when placed in water or under physiological conditions for a long time.Studies have shown that when placed in deionized water for 30 days,the weight of ANUC-2 hydrogel only increases by 7.2%.Therefore,ANUC hydrogel has strong anti-swelling ability.Due to the anti-swelling properties of ANUC hydrogel,it has excellent mechanical properties in different environments.For example,the mechanical properties of ANUC-2 are increased by 225.3%and 219.7%respectively when placed at p H=3 for 3 days and 5 days.As the hydrogel network is rearranged to form a denser network under different strong acids and weak bases,its mechanical properties are improved.In addition,the adhesion energy of ANUC-2 hydrogel on porcine skin was1349 J/m²,showing excellent wet adhesion ability.4.The adhesion efficiency of most common hydrogels is short-term and is often limited to ambient conditions,because water within the hydrogels readily transforms from liquid to solid and to vapor in response to changes in temperature.The hydrogels shall inevitably freeze at subzero temperatures and dry and harden due to water evaporation at ambient or high temperatures.These two cases would lead to loss of flexibility,adhesion,and toughness of the hydrogels.Inspired by the adhesion mechanism of mussel,for the first time,urushiol（UH）,a natural catechol derivative with a long alkyl side chain,is used as a starting material to copolymerize with acrylamide for fabricating tough,antifreezing/antiheating,wet adhesive hydrogels,The hydrophobic association andπ–πinteraction from UH moieties of the copolymer are greatly improved its mechanical strength（tensile stress:～0.12 MPa with strain of～1100%,toughness:～72 k J/m³,compression stress:～6.72 MPa at strain of 90%）.The hydrogel can strongly adhere to various dry/wet biological/polymeric/ceramic/metallic substrates at temperatures ranging from-45 to 50°C.Under ambient conditions,its adhesion force to porcine skin,glass,and tinplate may reach up to 160,425,and 275 N/m,respectively.Even stored at-45 or50°C for 4 months,the hydrogel still maintains good flexibility and robust adhesion force.the sustainability of expelling water from the substrate surface and shielding the catechol group from oxidation by the long hydrophobic alkyl chains is vital to the durable wet adhesion.In the fifth bonding-debonding cycle,only ca.19.0%and 10.0%reduction are incurred after five cycles on glass and tinplate,respectively.The adhesion force to glass can remain as high as 82%after 150 min of immersion in water.